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Summary This meta-analysis synthesized current evidence from 24 clinical trials to evaluate the impact of different resistance training modes on postmenopausal bone loss. Exercise interventions were categorized into two training modes, namely resistance-alone versus combined resistance training protocols. The combined resistance training protocols were defined as the combination of resistance training and high-impact or weight-bearing exercise. The results suggested that the combined resistance training protocols were effective in improving bone mineral density (BMD) at the femoral neck and lumbar spine. Introduction The current meta-analysis aimed to examine the effects of combined resistance and resistance-alone training protocols on the preservation of femoral neck and lumbar spine BMD in postmenopausal women. Methods An electronic database search was conducted in PubMed, EMBASE, SPORTDiscus, Web of Science, and ProQuest up to March 1, 2014 for the influence of resistance exercise on BMD in postmenopausal women. The study quality was evaluated. The effect sizes were estimated in terms of the standardized mean difference (SMD). A subgroup analysis was conducted by exercise categories. Results Twenty-four studies were included in the overall analysis of skeletal response to resistance exercise. The between-study heterogeneity was evident for the hip ( I 2  = 46.5 %) and spine ( I 2  = 62.3 %). The overall analysis suggested that resistance training significantly increased femoral neck BMD (SMD = 0.303, 95 % confidence interval (95 % CI) = 0.127–0.479, p  = 0.001) and lumbar spine BMD (SMD = 0.311, 95 % CI = 0.115–0.507, p  = 0.002) in postmenopausal women. However, subgroup analysis indicated that combined resistance training programs significantly affected both the hip BMD (SMD = 0.411, 95 % CI = 0.176–0.645, p  = 0.001) and spine BMD (SMD = 0.431, 95 % CI = 0.159–0.702, p  = 0.002), whereas resistance-alone protocols only produced nonsignificant positive effects both on the femoral neck and lumbar spine BMD. Conclusions Combined resistance exercise protocols appear effective in preserving femoral neck and lumbar spine BMD in postmenopausal women, whereas resistance-alone protocols only produced a nonsignificant positive effect.

The COVID-19 outbreak has raised numerous challenges for mental health service system in China. The pandemic has many affects on clinical, research and teaching, due to the strict quarantine in china. Fight the COVID-19 became the most important thing in work. We outlined major mental health needs during COVID-19 outbreak from the exiting studies and challenges for mental health professionals, and how to manage these challenges in China. To reduce the risk of negative psychological outcomes associated with the COVID-19 pandemic, the Central Health Authority of China and different national academic societies have integrated mental health crisis interventions into the general deployment of disease prevention and treatment. The NHCC developed a mental health triage strategy to provide four levels of psychological crisis interventions. More than 20 specific guidelines and expert consensus for mental health services for the COVID-19 outbreak were disseminated by the end of February 2020 to provide timely guidance for frontline health care professionals. External mental health expert teams in other provinces were also established to provide emergency mental health services in Hubei province, China. In addition, widespread adoption of online public education, psychological counseling, and hotline services have been set up for those in need. Although the COVID-19 pandemic has been under control in China, we should take a proactive lead to share its protocol of emergency mental health services with other countries affected by the COVID-19 pandemic. Also international cooperation is urgely needed to control the COVID-19 pandemic worldwide. Large-scale epidemiological surveys should be conducted to examine the prevalence of mental health problems associated with the COVID-19 pandemic to inform the development of appropriate mental health services in future.

We describe the baseline coupled model configuration and simulation characteristics of GFDL's Earth System Model Version 4.1 (ESM4.1), which builds on component and coupled model developments at GFDL over 2013–2018 for coupled carbon‐chemistry‐climate simulation contributing to the sixth phase of the Coupled Model Intercomparison Project. In contrast with GFDL's CM4.0 development effort that focuses on ocean resolution for physical climate, ESM4.1 focuses on comprehensiveness of Earth system interactions. ESM4.1 features doubled horizontal resolution of both atmosphere (2° to 1°) and ocean (1° to 0.5°) relative to GFDL's previous‐generation coupled ESM2‐carbon and CM3‐chemistry models. ESM4.1 brings together key representational advances in CM4.0 dynamics and physics along with those in aerosols and their precursor emissions, land ecosystem vegetation and canopy competition, and multiday fire; ocean ecological and biogeochemical interactions, comprehensive land‐atmosphere‐ocean cycling of CO2, dust and iron, and interactive ocean‐atmosphere nitrogen cycling are described in detail across this volume of JAMES and presented here in terms of the overall coupling and resulting fidelity. ESM4.1 provides much improved fidelity in CO2 and chemistry over ESM2 and CM3, captures most of CM4.0's baseline simulations characteristics, and notably improves on CM4.0 in (1) Southern Ocean mode and intermediate water ventilation, (2) Southern Ocean aerosols, and (3) reduced spurious ocean heat uptake. ESM4.1 has reduced transient and equilibrium climate sensitivity compared to CM4.0. Fidelity concerns include (1) moderate degradation in sea surface temperature biases, (2) degradation in aerosols in some regions, and (3) strong centennial scale climate modulation by Southern Ocean convection. Plain Language Summary GFDL has developed a coupled chemistry‐carbon‐climate Earth System Model (ESM4.1) as part of its fourth‐generation coupled model development activities with model results contributed publicly to the sixth phase of the Coupled Model Intercomparison Project. With similar computational expense as GFDL's first coupled model CM4.0, ESM4.1 focuses on chemistry and ecosystem comprehensiveness rather than the ocean resolution‐focus of CM4.0. With fidelity near to that of CM4.0, ESM4.1 features much improved representation of climate mean patterns and variability from previous GFDL ESMs as well as comprehensive couplings for chemistry, carbon, and dust. Key Points A new coupled chemistry‐carbon‐climate Earth system model has been developed at the Geophysical Fluid Dynamics Laboratory This model unifies component advances in chemistry, carbon, and ecosystem comprehensiveness within a single coupled climate framework This model features much improved climate mean patterns and variability from previous chemistry and carbon coupled models

Finely tuned optogenetic control of engineered Saccharomyces cerevisiae enhances the biosynthesis of valuable products such as isobutanol in laboratory-scale fermenters. Chemical production with pulses of light Optogenetics is a powerful method for the controlled study of biological systems based on light-sensitive proteins. Light offers a non-invasive alternative to classical methods and a versatile way of tuning a given system. In this study, José Avalos and colleagues used optogenetics to regulate engineered microbial metabolic processes. They used light to precisely control fermentation, applying periodic pulses to finely tune enzyme expression. The authors used this approach to produce two biofuels and feedstock chemicals, isobutanol and 2-methyl-1-butanol, from glucose in yeast with enhanced yields in bioreactors. The optimization of engineered metabolic pathways requires careful control over the levels and timing of metabolic enzyme expression 1 , 2 , 3 , 4 . Optogenetic tools are ideal for achieving such precise control, as light can be applied and removed instantly without complex media changes. Here we show that light-controlled transcription can be used to enhance the biosynthesis of valuable products in engineered Saccharomyces cerevisiae . We introduce new optogenetic circuits to shift cells from a light-induced growth phase to a darkness-induced production phase, which allows us to control fermentation with only light. Furthermore, optogenetic control of engineered pathways enables a new mode of bioreactor operation using periodic light pulses to tune enzyme expression during the production phase of fermentation to increase yields. Using these advances, we control the mitochondrial isobutanol pathway to produce up to 8.49 ± 0.31 g l −1 of isobutanol and 2.38 ± 0.06 g l −1 of 2-methyl-1-butanol micro-aerobically from glucose. These results make a compelling case for the application of optogenetics to metabolic engineering for the production of valuable products.

We describe the Geophysical Fluid Dynamics Laboratory's CM4.0 physical climate model, with emphasis on those aspects that may be of particular importance to users of this model and its simulations. The model is built with the AM4.0/LM4.0 atmosphere/land model and OM4.0 ocean model. Topics include the rationale for key choices made in the model formulation, the stability as well as drift of the preindustrial control simulation, and comparison of key aspects of the historical simulations with observations from recent decades. Notable achievements include the relatively small biases in seasonal spatial patterns of top‐of‐atmosphere fluxes, surface temperature, and precipitation; reduced double Intertropical Convergence Zone bias; dramatically improved representation of ocean boundary currents; a high‐quality simulation of climatological Arctic sea ice extent and its recent decline; and excellent simulation of the El Niño‐Southern Oscillation spectrum and structure. Areas of concern include inadequate deep convection in the Nordic Seas; an inaccurate Antarctic sea ice simulation; precipitation and wind composites still affected by the equatorial cold tongue bias; muted variability in the Atlantic Meridional Overturning Circulation; strong 100 year quasiperiodicity in Southern Ocean ventilation; and a lack of historical warming before 1990 and too rapid warming thereafter due to high climate sensitivity and strong aerosol forcing, in contrast to the observational record. Overall, CM4.0 scores very well in its fidelity against observations compared to the Coupled Model Intercomparison Project Phase 5 generation in terms of both mean state and modes of variability and should prove a valuable new addition for analysis across a broad array of applications. Plain Language Summary The Geophysical Fluid Dynamics Laboratory (GFDL) of the National Oceanic and Atmospheric Administration participates along with a number of model centers around the world in constructing state‐of‐the‐art climate models for use in studies for climate change and prediction. GFDL's latest multipurpose atmosphere‐ocean coupled climate model, CM4.0, is described here. It consists of GFDL's latest atmosphere and land models at about 100 km horizontal resolution and ocean and sea ice models at roughly 25 km horizontal resolution. A handful of standard experiments have been conducted with CM4.0 for participation in the Coupled Model Intercomparison Project Phase 6, an archive of climate model results utilized by the Intergovernmental Panel on Climate Change and the climate research community more generally. The model results have been extensively evaluated against observations. This paper makes the case that CM4.0 ranks high among state‐of‐the‐art coupled climate models by many measures of bias in the simulated climatology and in its ability to capture modes of climate variability such as the El Niño‐Southern Oscillation and Madden‐Julian Oscillation. The paper also discusses some potential weaknesses, including unrealistically large internal variability in the Southern Ocean and insufficient warming before 1990 in the simulation of the twentieth century. Key Points A team at GFDL has developed a new model of the physical climate system referred to as CM4.0 Strengths of model include ENSO simulation and small biases in TOA fluxes, precipitation, Arctic sea ice extent, and sea surface temperature Problematic aspects include large variability in Southern Ocean and historical simulation with little warming prior to 1990

To maximize a desired product, metabolic engineers typically express enzymes to high, constant levels. Yet, permanent pathway activation can have undesirable consequences including competition with essential pathways and accumulation of toxic intermediates. Faced with similar challenges, natural metabolic systems compartmentalize enzymes into organelles or post-translationally induce activity under certain conditions. Here we report that optogenetic control can be used to extend compartmentalization and dynamic control to engineered metabolisms in yeast. We describe a suite of optogenetic tools to trigger assembly and disassembly of metabolically active enzyme clusters. Using the deoxyviolacein biosynthesis pathway as a model system, we find that light-switchable clustering can enhance product formation six-fold and product specificity 18-fold by decreasing the concentration of intermediate metabolites and reducing flux through competing pathways. Inducible compartmentalization of enzymes into synthetic organelles can thus be used to control engineered metabolic pathways, limit intermediates and favor the formation of desired products. Optogenetically controlling the assembly of enzyme clusters enhances product formation and specificity during deoxyviolacein biosynthesis by decreasing concentrations of intermediate metabolites and reducing flux through competing pathways.

In this study, We demonstrated that Bax mitochondrial translocation plays a vital role in the initiation of the mitochondrial signaling pathway upon activation by heat stress. In addition, both p53 mitochondrial translocation and Ca 2+ signal mediated MPTP opening activate Bax mitochondrial translocation. Employing pifithrin-α (a p53 mitochondrial translocation inhibitor) and CsA (a permeability transition pore (MPTP) inhibitor), we found that heat stress induced Bax mitochondrial translocation was significantly inhibited in cells pretreated with both PFT and CsA. Furthermore, we demonstrated that generation of reactive oxygen species (ROS) is a critical mediator in heat stress induced apoptosis and that the antioxidant MnTBAP significantly decreased heat stress induced p53 mitochondrial translocation and Ca 2+ signal mediated MPTP opening, as well as the subsequent Bax mitochondrial translocation and activation of the caspase cascade. Taken together, our results indicate that heat stress induces apoptosis through the mitochondrial pathway with ROS dependent mitochondrial p53 translocation and Ca 2+ dyshomeostasis and the ensuing intro Bax mitochondrial translocation as the upstream events involved in triggering the apoptotic process observed upon cellular exposure to heat stress.

Control of the lac operon with isopropyl β- d -1-thiogalactopyranoside (IPTG) has been used to regulate gene expression in Escherichia coli for countless applications, including metabolic engineering and recombinant protein production. However, optogenetics offers unique capabilities, such as easy tunability, reversibility, dynamic induction strength and spatial control, that are difficult to obtain with chemical inducers. We have developed a series of circuits for optogenetic regulation of the lac operon, which we call OptoLAC, to control gene expression from various IPTG-inducible promoters using only blue light. Applying them to metabolic engineering improves mevalonate and isobutanol production by 24% and 27% respectively, compared to IPTG induction, in light-controlled fermentations scalable to at least two-litre bioreactors. Furthermore, OptoLAC circuits enable control of recombinant protein production, reaching yields comparable to IPTG induction but with easier tunability of expression. OptoLAC circuits are potentially useful to confer light control over other cell functions originally designed to be IPTG-inducible. Reengineering of the lac operon in E. coli from a ligand-inducible to a blue-light-regulated gene expression system facilitates optogenetic control of biotechnological applications including metabolic engineering and protein expression.

In low-dimensional electron systems, charge density waves (CDW) and superconductivity are two of the most fundamental collective quantum phenomena. For all known quasi-two-dimensional superconductors, the origin and exact boundary of the electronic orderings and superconductivity are still attractive problems. Through transport and thermodynamic measurements, we report on the field-temperature phase diagram in 2 H -TaS 2 single crystals. We show that the superconducting transition temperature ( T c ) increases by one order of magnitude from temperatures at 0.98 K up to 9.15 K at 8.7 GPa when the T c becomes very sharp. Additionally, the effects of 8.7 GPa illustrate a suppression of the CDW ground state, with critically small Fermi surfaces. Below the T c the lattice of magnetic flux lines melts from a solid-like state to a broad vortex liquid phase region. Our measurements indicate an unconventional s -wave-like picture with two energy gaps evidencing its multi-band nature.

The vasopressin 1b receptor (Avpr1b) is critical for social memory and social aggression in rodents, yet little is known about its specific roles in these behaviors. Some clues to Avpr1b function can be gained from its profile of expression in the brain, which is largely limited to the pyramidal neurons of the CA2 region of the hippocampus, and from experiments showing that inactivation of the gene or antagonism of the receptor leads to a reduction in social aggression. Here we show that partial replacement of the Avpr1b through lentiviral delivery into the dorsal CA2 region restored the probability of socially motivated attack behavior in total Avpr1b knockout mice, without altering anxiety-like behaviors. To further explore the role of the Avpr1b in this hippocampal region, we examined the effects of Avpr1b agonists on pyramidal neurons in mouse and rat hippocampal slices. We found that selective Avpr1b agonists induced significant potentiation of excitatory synaptic responses in CA2, but not in CA1 or in slices from Avpr1b knockout mice. In a way that is mechanistically very similar to synaptic potentiation induced by oxytocin, Avpr1b agonist-induced potentiation of CA2 synapses relies on NMDA (N-methyl-D-aspartic acid) receptor activation, calcium and calcium/calmodulin-dependent protein kinase II activity, but not on cAMP-dependent protein kinase activity or presynaptic mechanisms. Our data indicate that the hippocampal CA2 is important for attacking in response to a male intruder and that the Avpr1b, likely through its role in regulating CA2 synaptic plasticity, is a necessary mediator.